Ma Liuheyi, Zuo Xiaoyu, Lu Bingtai, Zhang Yuxia
School of Medicine, South China University of Technology, Guangzhou, 510006, China.
Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510623, China.
BMC Genom Data. 2025 May 1;26(1):33. doi: 10.1186/s12863-025-01306-5.
Pneumonia is a major cause of mortality and health burden in children under five, yet its genetic etiology remains poorly understood. Methyltransferase 4, N6-adenosine (METTL4), is a methyltransferase enzyme responsible for RNA and DNA methylation and is known to be activated under hypoxic conditions. However, its potential link to susceptibility to pneumonia has not been evaluated. This study aimed to explore candidate regulatory single nucleotide polymorphisms (SNPs) within the METTL4 gene and their association with the development of severe pneumonia.
In this study, we recruited a cohort of 1034 children with severe pneumonia and 8426 healthy controls. We investigated the associations of candidate regulatory single nucleotide polymorphisms (SNPs) within METTL4 polymorphisms with severe pneumonia. Our results indicated that the C allele of rs9989554 (P = 0.00023, OR = 1.21, 95% CI: 1.09-1.34) and the G allele of rs16943442 (P = 0.0026, OR = 1.22, 95% CI: 1.07-1.38) were significantly associated with an increased risk of severe pneumonia. The regulatory potential of these two SNPs in the lung was investigated using tools such as expression quantitative trait loci (eQTLs), RegulomeDB, and FORGEdb.
This study represents the first investigation elucidating the role of genetic variations in the METTL4 gene and their influence on susceptibility to severe pneumonia in pediatric populations. METTL4 is identified as a novel predisposing gene for severe pneumonia and a potential therapeutic target. Further research is warranted to validate this correlation and to comprehensively elucidate the biological role of the METTL4 gene in severe pneumonia.
肺炎是五岁以下儿童死亡和健康负担的主要原因，但其遗传病因仍知之甚少。甲基转移酶4，N6-腺苷（METTL4）是一种负责RNA和DNA甲基化的甲基转移酶，已知在缺氧条件下被激活。然而，其与肺炎易感性的潜在联系尚未得到评估。本研究旨在探索METTL4基因内的候选调控单核苷酸多态性（SNP）及其与重症肺炎发生的关联。
在本研究中，我们招募了1034名重症肺炎儿童和8426名健康对照。我们研究了METTL4基因多态性内候选调控单核苷酸多态性（SNP）与重症肺炎的关联。我们的结果表明，rs9989554的C等位基因（P = 0.00023，OR = 1.21，95% CI：1.09 - 1.34）和rs16943442的G等位基因（P = 0.0026，OR = 1.22，95% CI：1.07 - 1.38）与重症肺炎风险增加显著相关。使用表达数量性状位点（eQTL）、RegulomeDB和FORGEdb等工具研究了这两个SNP在肺中的调控潜力。
本研究首次阐明了METTL4基因遗传变异在儿科人群中对重症肺炎易感性的作用及其影响。METTL4被确定为重症肺炎的一个新的易感基因和潜在治疗靶点。有必要进行进一步研究以验证这种相关性，并全面阐明METTL4基因在重症肺炎中的生物学作用。
